1. Field
This disclosure relates to an apparatus for stimulating the brain and measuring the light induced neuronal activity capable of stimulating the brain during an experiment on a living body and of minimizing damage to the brain during insertion of the apparatus. Further, this disclosure relates to an apparatus capable of improving measuring efficiency by approximating the site where the stimulation is applied to the site where the measurement is made.
2. Description of the Related Art
Neuropsychiatric diseases are known to develop in the neural circuit level starting from the abnormality of specific neural cells (neurons). For example, Parkinson's disease is known to result from the loss of dopaminergic neurons in the substantia nigra. For the treatment of neuropsychiatric diseases, operations such as deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), etc. are performed in addition to medication. These methods are disadvantageous in that it is difficult to treat the diseases elaborately and systematically in the signaling level of the neural circuit.
Recently, in the field of brain research, light-sensitive proteins have been developed, which react in response to light of specific wavelength to activate or inhibit neurons. Using them, it is possible to control the neurons in the neural circuit more freely and elaborately. The past electrical-type micro-stimulants had several limitations as follows. First, due to the heterogeneity of brain tissue, it is unclear which circuit elements are responsible for the therapeutic effects. Second, the electrical-type micro-stimulant is intrinsically a complicated manipulation because target neurons can respond with increased, decreased, or mixed temporal patterns of activity; as a result the magnitude and even the sign of target cell responses to the electrical stimulants are unknown. Finally, it is difficult to assess the net outcome of the electrical-type micro-stimulants on overall activity in the target cells and region, because electrical stimulation creates artifacts that prevent direct observation of local circuit responses during the electrical stimulation itself.
In contrast, optical stimulation of neurons is advantageous in that the target neurons can be freely selected by using different promoters. In addition, once the light-sensitive protein is expressed in the target neurons, activation and inhibition thereof can be controlled freely by controlling the wavelength range of the optical stimulation. Therefore, the optical stimulation allows more elaborate and systematic study of the neural circuit. Further, it helps to understand what specific brain neurons are related with a particular neuropsychiatric disease and how a problem occurs in the neural circuit.
In technical sense, to realize the optical stimulation of neurons in a living body (in vivo), it is very important to insert an optic fiber in the brain more stably. Further, in many cases, a recording electrode is inserted together in order to verify whether the light-sensitive protein was sufficiently expressed in the target area of the neurons. In experiments using small animals such as mouse, there is a high risk of damage to the brain during the insertion of this electrode-coupled optic fiber. Moreover, in the actually inserted optic fiber and a electrode couple, the site at which optical stimulation is applied by the light emitted from the optic fiber is not identical to the site of measurement (distant by about 0.125 mm (millimeter) or more). As a result, the measuring efficiency of the activation and inhibition of neurons by the optical nerve stimulation is very low.
Accordingly, there is a need of an apparatus for stimulation and detection capable of performing optical stimulation of neurons stably and efficiently, and a method for manufacturing the same.